Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes: Gefitinib Used as a Probe Substrate in Rats.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6.

Effects of antibiotics on the pharmacokinetics of indoxyl sulfate, a nephro-cardiovascular toxin.

Indoxyl sulfate (IS), a highly protein-bound nephro-cardiovascular toxin, was poorly removed by hemodialysis. IS exists as anions in the body and the renal excretion is mediated by organic anion transporter 1 (OAT1) and OAT3. Acidic antibiotics such as cephalosporins and fluoroquinolones were putative substrates/inhibitors of OATs.

Effects of nonsteroidal anti-inflammatory drugs on the renal excretion of indoxyl sulfate, a nephro-cardiovascular toxin, in rats.

Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3.

R- and S-Warfarin Were Transported by Breast Cancer Resistance Protein: From In Vitro to Pharmacokinetic-Pharmacodynamic Studies.

Warfarin, a racemate of R- and S-warfarin, is an important oral anticoagulant with narrow therapeutic window. Being an acidic drug, warfarin (pKa = 4.94) exists mainly as anion under physiological pH.

Aloe activated P-glycoprotein and CYP 3A: a study on the serum kinetics of aloe and its interaction with cyclosporine in rats.

Aloe, the leaf juice of Aloe vera, is a popular functional food worldwide. The major constituents of aloe are polyphenolic anthranoids such as aloin, aloe-emodin and rhein. Cyclosporine (CSP), an immunosuppressant with a narrow therapeutic window, is a probe substrate of P-glycoprotein (P-gp), an efflux pump, and CYP 3A4.

Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure.

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3.

Tissue distribution of naringenin conjugated metabolites following repeated dosing of naringin to rats.

Background: Naringin is a major antioxidant in fruits and herbs. To clarify molecular forms distributed to various tissues, we investigated tissue distribution of naringin and relevant metabolites in rats after repeated dosing. Methods: Male Sprague-Dawley rats were orally administered naringin (210 mg/kg) twice daily for eight days.

Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies.

Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window.

Serum concentrations of anthraquinones after intake of Folium Sennae and potential modulation on P-glycoprotein.

Folium Sennae (leaves of Cassia angustifolia or senna) is a laxative and a component in diets for weight control. It contains a variety of anthranoids such as sennosides, aloe-emodin, and rhein. In order to measure the serum concentrations of senna anthranoids, Sprague-Dawley rats were orally administered with single dose and multiple doses of Folium Sennae.

Interaction of rhubarb and methotrexate in rats: in vivo and ex vivo approaches.

Rhubarb, the rhizome of Rheum palmatum L. (RP), is a popular herb used in Chinese medicine prescriptions. RP contains a variety of polyphenolic anthraquinones, such as aloe-emodin, rhein, emodin and chrysophanol.

Potential risk of mulberry-drug interaction: modulation on P-glycoprotein and cytochrome P450 3A.

Mulberry is a fruit containing polyphenol antioxidants. Cyclosporine (CSP), a potent immunosuppressant with a narrow therapeutic range, is widely used in transplant patients. This study investigated the effect of co-administration of mulberry on the bioavailability of CSP, a probe drug of P-glycoprotein (P-gp)/cytochrome P450 3A4 (CYP 3A4), in rats and relevant mechanisms.

A Chinese herb formula decreases the monocarboxylate transporter-mediated absorption of valproic acid in rats.

Huang-Qin-Tang (HQT), a Chinese medicine prescription containing Scutellariae Radix (SR), Paeoniae Radix (PR), Glycyrrhizae Radix (GR) and JuJubae Fructus (JF), was used for the treatments of cold with symptoms of abdominalgia and diarrhea. Valproic acid (VPA) is an antiepileptic drug with narrow therapeutic window. This study investigated the effect of coadministration of HQT on the pharmacokinetics of VPA, a probe drug for monocarboxylate transporter (MCT).

Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A.

Liquorice (root of Glycyrrhiza uralensis FISCH) is an ingredient of candies and used as a popular medicine in Europe and oriental countries. Cyclosporine (CsA), an immunosuppressant with narrow therapeutic window, is widely used in transplant patients. The absorption and disposition of CsA were associated with P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4).

Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction.

The rhizome of Rheum palmatum (RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats.

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window.

Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes.

Ethnopharmacological Relevance: The Ger-Gen-Chyn-Lian-Tang (GGCLT), an officially standardized mixture of Chinese herbal medicines, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma and Glycyrrhizae Radix in a ratio of 8:3:3:2. In this study, we evaluated the benefits of GGCLT in atherosclerotic progression.

Methods: The major constituents of GGCLT were analyzed by HPLC.

Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: an ex vivo approach.

In recent years much attention has been focused on the pharmaceutical relevance of bioflavonoids, especially hesperidin and its aglycon hesperetin in terms of their antioxidant and anti-inflammatory actions. However, the bioactivity of their metabolites, the real molecules in vivo hesperetin glucuronides/sulfates produced after ingestion, has been poorly understood. Thus, the study using an ex vivo approach is aimed to compare the antioxidant and anti-inflammatory activities of hesperidin/hesperetin or hesperetin metabolites derived from hesperetin-administered rat serum.

Citrus grandis peel increases the bioavailability of cyclosporine and tacrolimus, two important immunosuppressants, in rats.

Citrus grandis peel (CGP) is a beverage ingredient and a medicinal herb in Oriental countries. Cyclosporine and tacrolimus, important immunosuppressants with narrow therapeutic windows, are widely used in transplant patients. This study investigated the effects of co-administering CGP on the bioavailability of cyclosporine and tacrolimus.

Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats.

Aim Of The Study: Rhei Rhizoma, the rhizome of Rheum palmatum L. (RP), is a popular herb in clinical Chinese medicine. RP is abundant in polyphenolic anthraquinones, which have been reported to show various beneficial bioactivities.

Pharmacokinetics, bioavailability, and tissue distribution of magnolol following single and repeated dosing of magnolol to rats.

Magnolol (M) is a polyphenol antioxidant abundant in the bark of Magnolia officinalis Rehder & E. Wilson, a popular Chinese herb. To understand the pharmacokinetics and bioavailability of M, Sprague-Dawley rats were intravenously injected with a bolus of M (20 mg/kg) and orally given a single dose and seven doses of M (50 mg/kg).

Neocarzinostatin as a probe for DNA protection activity--molecular interaction with caffeine.

Neocarzinostatin (NCS), a potent mutagen and carcinogen, consists of an enediyne prodrug and a protein carrier. It has a unique double role in that it intercalates into DNA and imposes radical-mediated damage after thiol activation. Here we employed NCS as a probe to examine the DNA-protection capability of caffeine, one of common dietary phytochemicals with potential cancer-chemopreventive activity.

Quercetin and rutin reduced the bioavailability of cyclosporine from Neoral, an immunosuppressant, through activating P-glycoprotein and CYP 3A4.

Quercetin and rutin are popular flavonoids in plant foods, herbs, and dietary supplements. Cyclosporine (CSP), an immunosuppressant with a narrow therapeutic window, is a substrate of P-glycoprotein (P-gp) and cytochrome P-450 3A4 (CYP3A4). This study investigated the effects of quercetin and rutin on CSP pharmacokinetics from Neoral and relevant mechanisms.

Different influences on tacrolimus pharmacokinetics by coadministrations of zhi ke and zhi shi in rats.

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine.

Suppression on metastasis by rhubarb through modulation on MMP-2 and uPA in human A549 lung adenocarcinoma: an ex vivo approach.

Aim Of The Study: The aim of this study is to determine and identify the possible molecular mechanisms of anti-cancer effect of rhubarb under the physiologically achievable concentrations by using an ex vivo approach.

Materials And Methods: Rats were orally administered rhubarb decoction and then serum metabolites were extracted, prepared and characterized to assay for the following in vitro study. The MTT assay, zymography analysis, wound healing assay, RT-PCR, and Western blot analysis were used to reveal molecular events of rhubarb metabolites in this study.